A defect in l-isoleucine metabolism associated with α-methyl-β-hydroxybutyric and α-methylacetoacetic aciduria: Quantitative in vivo and in vitro studies

Abstract A patient is described with α-methylacetoacetic and α-methyl-β-hydroxybutyric aciduria. These acids, as their coenzyme A esters are intermediates in the degradation of isoleucine. Synthesis of these metabolites has allowed quantitative studies to be performed following isoleucine loading tests. An in vitro assay has been established to measure the isoleucine degradation pathway from tiglyl-CoA to propionyl-CoA in broken leucocyte preparations. Leucocytes from the patient had a diminished activity of this section of the pathway, indicating that the excretion of the abnormal metabolites is probably due to a primary enzyme defect in isoleucine degradation, rather than a secondary enzyme inhibition.